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Avira Antivirus Pro - Review 2020 - PCMag India

Avira Antivirus Pro - Review 2020 - PCMag IndiaAvira Antivirus Pro - Review 2020 - PCMag IndiaPosted: 11 Jun 2020 12:00 AM PDTEvery computer needs antivirus protection, and one way companies can support that aim is to provide free antivirus to the masses. But these companies can't survive unless some users shell out their hard-earned cash for paid antivirus utilities. Piling on pro-only tools and components is one way companies encourage upgrading to a paid antivirus. Avira Antivirus Pro adds several components not available to users of Avira Free Security, but they don't really add much value. The biggest reason to pay for it is if you want to use Avira in a commercial setting, which isn't allowed with the free version.Avira's pricing is undeniably on the high side, with a list price of $59.88 per year for one license, $71.88 for three, and $95.88 for five. Admittedly, it seems to be perpetually on sale; just now, the one-license price is discounted to $44.99. That…

COVID-19: Scientists identify promising drug candidates - Medical News Today

COVID-19: Scientists identify promising drug candidates - Medical News Today

COVID-19: Scientists identify promising drug candidates - Medical News Today

Posted: 09 May 2020 12:00 AM PDT

By mapping interactions between human proteins and the new coronavirus, researchers have pinpointed 29 potential treatments using drugs already approved by the Food and Drug Administration (FDA) for a wide range of other conditions.

close up of scientist's hands working with a pipette in labShare on Pinterest
Scientists have tested an array of pre-existing drugs to see how they might tackle the new coronavirus.

All data and statistics are based on publicly available data at the time of publication. Some information may be out of date.

There is currently no vaccine or antiviral drug with proven efficacy against SARS-CoV-2, the virus that causes COVID-19, though several clinical trials are underway.

Lack of in-depth knowledge about how the newly emerged virus interacts with human cells has hampered the hunt for an effective treatment.

A study set for publication in the journal Nature marks a significant leap forward in our understanding of the interaction between the virus and its host. An unedited PDF of the peer-reviewed paper is available for download.

Prof. Nevan J. Krogan, from the University of California San Francisco (UCSF), is the last author of the study.

The research also identifies dozens of potential drug candidates, including 29 already approved by the FDA for treating cancer, type 2 diabetes, and schizophrenia, among other conditions.

Viruses work by hijacking the machinery of their host cell to make copies of themselves, which can then go on to infect other cells.

Prof. Krogan and team write:

"To devise therapeutic strategies to counteract SARS-CoV-2 infection … it is crucial to develop a comprehensive understanding of how this coronavirus hijacks the host during the course of infection, and to apply this knowledge towards developing both new drugs and repurposing existing ones."

In 2011, Prof. Nevan Krogan and his colleagues at UCSF discovered a way to map all the human proteins that a virus needs to survive and replicate.

The idea is that drugs targeting these proteins can potentially disrupt the replication of the virus.

The technique, which they call affinity purification mass spectrometry, involves first synthesizing genes from the virus and then injecting them into human cells in the lab.

The first protein "interactome" map they created was for HIV and led to the development of one of the drugs in the cocktail used to treat the virus.

The researchers have also mapped the viruses that cause Ebola, dengue fever, Zika virus, West Nile fever, and several other diseases.

Early this year, the scientists led a collaboration of 22 labs in the United States, France, and the United Kingdom that worked around the clock to complete a protein interactome map for SARS-CoV-2.

"This was a huge effort led by Nevan Krogan's team at UCSF," says Prof Bryan L. Roth, MD, Ph.D. of the University of North Carolina School of Medicine in Chapel Hill, NC, which was part of the collaboration. "It is amazing this team of 100 researchers completed this so fast, given that the genetic sequence of the virus was not available for study until January."

They identified 332 interactions between human and viral proteins. Among the human proteins involved in these interactions, 66 are targeted by 69 known compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 in preclinical development).

When the researchers screened these compounds in human cell cultures, most did not affect the virus. However, they discovered some potent ones, which fell into two groups.

Some of the drugs inhibited protein production, while others interacted with regulators of a pair of receptor proteins known as Sigma1 and Sigma2.

Some of the drug candidates are antibiotics that are known to kill bacteria by disrupting the cellular machinery they use to build their proteins.

Two other candidates are the antimalarial chloroquine and hydroxychloroquine, which bind to the sigma1 receptor.

Doctors, scientists, and other experts have shown considerable interest in using these antimalarials to treat severe COVID-19. Unfortunately, these drugs also bind to several other human proteins, which make them toxic at high doses, according to an original investigation published in JAMA Network.

In particular, they bind to the protein hERG, which can trigger potentially fatal cardiac arrhythmia. Last week, the Food and Drug Administration (FDA) issued a warning about the dangers of using chloroquine and hydroxychloroquine for treating COVID-19.

Chloroquine, in particular, has sparked significant controversy around its use for COVID-19. In their Nature paper, Prof. Krogan and the team found that other compounds target the new coronavirus in a more promising way — such as the anticancer drug PB28.

Prof. Krogan and the team report that a variety of other FDA-approved drugs also target the sigma receptors. The drugs include progesterone, some drugs used to treat allergies, and the antipsychotic haloperidol.

They write that the most promising drug is an experimental anticancer drug called PB28. They found the drug was 20 times more potent than hydroxychloroquine at deactivating the new coronavirus.

Unlike the two antimalarials, PB28 does not bind to the hERG protein. This means that it may be safer at high doses.

Prof. Krogan told the New York Times that scientists have already begun some animal studies to test whether PB28 lives up to its early promise.

A large, unintentional trial of many of the drugs that Prof. Krogan and his team identified is already underway. Because doctors are already treating many COVID-19 patients with these drugs for unrelated conditions, it will be informative to see whether a pattern emerges in their survival rates.

They write: "Many COVID-19 patients will be on the drugs identified here, treating pre-existing conditions. It may be useful to correlate clinical outcomes with the taking of these drugs, cross-referencing with the networks described here."

In their work with SARS-CoV-2 and other viruses, the researchers have uncovered shared mechanisms that the pathogens use to co-opt their host's molecular machinery in the course of infection.

They speculate that this may mean that scientists can identify drugs that are effective against a wide range of viruses. These could even include future infections that, like the coronaviruses, have jumped from animals into humans and have the potential to cause the next pandemic.

One important limitation of the new research is that scientists carried it out in cell cultures in the lab. Large clinical trials are needed to prove a drug's safety and efficacy in patients.

Nonetheless, the fact that the FDA have already approved these drugs for use in other diseases gives them a headstart.

Another caveat that the researchers note in their preprint is that some of the interactions between viral proteins and human proteins identified could be part of the cells' own attempt to fight off infection.

"It is important to note that pharmacological intervention with the agents we identified in this study could be either detrimental or beneficial for infection," they write.

In other words, some of these drugs could make the progress of COVID-19 worse, so the drugs should only be tested under very tightly controlled clinical research conditions.

For live updates on the latest developments regarding the novel coronavirus and COVID-19, click here.

'Something we've never seen before': Scientists still trying to understand baffling, unpredictable coronavirus - USA TODAY

Posted: 18 May 2020 04:01 AM PDT


Dr. Anthony Fauci told senators "it is without a doubt that there will be infections" in the fall and warned of more deaths without adequate response. USA TODAY

MILWAUKEE – The new coronavirus has spread like wildfire, killed – and spared – people of all ages and all health conditions, baffled doctors, defied guidance and conventional wisdom, and produced an unprecedented array of symptoms.

There's never been a virus like it.

"This gets into every major biological process in our cells," said Nevan J. Krogan, a molecular biologist at the University of California, San Francisco, who has studied HIV, Ebola, Zika, dengue and other viruses over the past 13 years.

"At the molecular level, it's something we've never seen before, and then look at what it does to the body – the long list of symptoms – we've never seen that before."

As Americans debate the reopening of businesses, bars, schools and other aspects of everyday life, it's important to understand the virus we are up against and why it has sown so much suffering and confusion.

At first, the virus was thought to be mostly a risk to older adults and people with chronic illnesses; its primary point of attack, the lungs. Then 30- and 40-years-olds with the virus began dying of strokes. Recently, a small number of infected children have died of a mysterious illness resembling Kawasaki disease.  

'Like a war': Pfizer head of vaccines talks finding a treatment for coronavirus

Symptoms of COVID-19 range from fever, coughing and shortness of breath to the loss of smell and taste and the angry red swelling that has come to be known as "COVID toes." Studies have found that damage from SARS-CoV-2, the virus that causes the disease COVID-19, isn't limited to the lungs; it can include the heart, liver, kidneys, gastrointestinal system and bowels. 

To understand a virus' "motivation" – why it does what it does – keep in mind that it is a parasite. It lives inside its human or animal host taking what it needs at the expense of the host.

As long as it finds hosts without immunity, and as long as its own mutations do not weaken its ability to spread and multiply, the virus thrives.

Key benchmarks of a virus are how widely it spreads and how deadly it is to those it infects.

In the five months since it was first identified in Wuhan, China, SARS-CoV-2 has infected more than 4.5 million people across the globe, killing more than 300,000.

"The thing that strikes me about the clinical aspect is the shear amount of transmissibility," said Megan Freeman, a virologist and specialist in pediatric infectious diseases at UPMC Children's Hospital of Pittsburgh.

"There are very few viruses that are more contagious than this one," agreed Mark Schleiss, an investigator for the Institute of Molecular Virology at the University of Minnesota.

A single COVID-19 patient spreads the disease to a median of 5.7 people, making it twice as contagious as the 1918 Spanish flu, according to a report in the journal Emerging Infectious Diseases.

A death crisis in New Jersey: How one mortician races to keep up with COVID-19

The rate of infection in the U.S. – what experts are referring to when they talk about  "flattening the curve" – has slowed. Even so, the nation is still averaging about 1,000 COVID-19 deaths a day, roughly twice the number of deaths from 9/11 every week.

Thousands of the world's best scientists have worked with remarkable speed seeking to understand the new coronavirus. They deciphered its genetic code in barely a week and have produced scores of papers suggesting possible treatments and vaccines. 

"The canvas we call COVID-19 was blank 16 weeks ago," said Gregory Poland, director of Mayo Clinic's Vaccine Research Group. "We've filled in a lot of dots, but we have so much more to go."

"We don't understand HIV that well in my opinion," Krogan said, "and we've been studying that for decades."  

Seeking the Achilles' heel of the virus

Scientists know some but not all of the reasons the new coronavirus spreads so easily. Freeman points to several factors, including one that distinguishes SARS-CoV-2 from the virus it closely resembles, Severe Acute Respiratory Syndrome (SARS).

SARS attacks the lower respiratory system, whose job it is to pull in air from the upper respiratory system.

SARS-CoV-2, however, attacks the upper respiratory system, the pathway that allows air to travel in and out of the lungs as we breathe. The upper airway is also the system involved when we cough.

The upper respiratory system offers a more efficient means of spreading, Freeman said.

"That's why it is more transmissible. ... When this emerged probably there was some mutation that adapted it to use the upper airway, and the upper airway has made it very successful."

A second difference between SARS and SARS-CoV-2 involves the bond that allows viral cells to attach to human cells and infect them. With both viruses, this bond forms between the Spike Protein on the virus and a region on the outside of the human cell called the ACE-2 receptor.

Both viruses use this bond to enter cells, but the bond is much stronger with the new coronavirus than it was with SARS. That is why many of the potential treatments so far are designed to undermine that bond.

"You always want to target the Achilles' heel of the virus, something the virus does not have the luxury of changing too much" explained Maria Elena Bottazzi, a professor of pediatrics at Baylor College of Medicine and co-developer of a potential SARS vaccine that is going to be tested on SARS-CoV-2.

Although public health leaders compared the new coronavirus to seasonal flu early on, coronaviruses have a special feature that separates them from other viruses like flu. They have their own proofreading system that helps limit mistakes in their genetic code known as mutations.

"Flu viruses make six and a half times more mistakes than coronaviruses do," Freeman said.

Even as the spread of the virus slows in the United States, some researchers fear what will happen if major outbreaks hit poorer, densely populated cities in Africa.

"Look at the problems we've had," Poland warned. "Now amplify that through areas that have civil wars, that have corruption, that have scarce resources. That's a humanitarian disaster in the making." 

A remarkable destroyer

The virus' skill at spreading poses one challenge; what it does inside the human body poses another. 

Much of what scientists have learned so far about the new coronavirus suggests that it is a remarkable destroyer at both the micro and macro levels, decimating individual cells and entire organs.

At the molecular level, the virus disrupts some of the most fundamental functions of life: cell division; the system cells use to talk with one another; and their ability to make proteins.

The proteins our bodies make help us carry out almost every human action from eating and walking to breathing and thinking.

Once a person ingests the new coronavirus, it enters the lungs and directly infects the air sacs, the microscopic workhorses that take in the air we breathe. In serious cases, the air sacs fill with fluid, leaving less and less room for oxygen. This is a feature of what is known as COVID-19 pneumonia.

The pneumonia can lead to Acute Respiratory Distress Syndrome, a severe breathing condition that deprives the vital organs of oxygen.

A healthy blood oxygen level is usually between 95% and 100%. Below 90% is low. Some COVID-19 patients have been found to have blood oxygen levels below 65%.

As the air sacs are infected and damaged, this triggers the immune system, which can lead to a dangerous condition called a cytokine storm. In a cytokine storm, the immune system goes into overdrive and winds up killing both healthy and diseased cells.

One of the most subtle and deadly offshoots of low blood oxygen is a condition called silent hypoxia.

As described by emergency room doctor Richard Levitan in a commentary in The New York Times, silent hypoxia allows patients to develop low blood oxygen levels without realizing the problem until it dips into dangerous territory. They breathe faster to compensate for the lack of oxygen but are unaware they are breathing faster.

Levitan suggested that people can bypass long waits for coronavirus tests, using a simple device called a pulse oximeter as an early warning system for detecting COVID-19 pneumonia. The device, which fits over your finger, measures blood oxygen levels, and can be bought at pharmacies without prescription for about $30.

Unfortunately, SARS-CoV-2 does not restrict its damage to the lungs.

The virus also causes blood clots, which have led to people in their 30s and 40s dying from strokes.

And then there are the recent cases in New York and Paris of children with COVID-19 who develop symptoms closely resembling Kawasaki disease. The disease begins with a rash and fever, inflames blood vessels, and eventually can damage the coronary arteries that deliver blood to the heart.

"What is it about COVID-19 that it produces Kawasaki disease?" said Schleiss, at the University of Minnesota, who estimates he has seen more than 1,000 Kawasaki cases in his medical career.

"I don't think SARS-CoV-2 is a cause of Kawasaki disease, but it is the cause of something very similar."

Every few weeks, SARS-CoV-2 seems to reveal new and disturbing oddities.

A recent study from China published in the journal JAMA Network Open, reported finding the new coronavirus in the semen of six of 38 infected men, raising concern that it may be possible to transmit the virus through sexual contact.

The virus also has been found in patient stool samples and untreated wastewater. The Centers for Disease Control and Prevention has reported that standard methods at wastewater treatment plants should be effective enough to protect workers.

Such discoveries, however, raise fundamental questions, as we try to return to our old lives. Have we yet determined all of the ways the virus can spread from one person to another? Are there activities that may pose risks we have not anticipated?

At the University of California, San Francisco, Krogan said it will be important to examine the genetic scripts of both those who suffer severe cases of COVID-19 and those who get mild or no disease at all.

"There are 30-year-olds and some of them are asymptomatic and others are on respirators. What the hell is that all about?" 

Follow Mark Johnson on Twitter: @majohnso


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